How kinases control membrane trafficking
We investigate how membranes of the secretory pathway are regulated by signal transduction pathways. Here, we are particularly interested in the role of the protein kinase D family. Specifically, we address how external cues control PKD activity and how the kinase engages its interactors and substrates to coordinate the secretory pathway.
Ultimately, we aim at determining the relevance of PKD in cell growth, polarity, migration and invasion, and stem cell maintenance to understand the impact of dys-regulation of PKD signaling and secretion in human diseases such as cancer and neurodegeneration.
Cell line engineering for improved production of therapeutic proteins
Chinese hamster ovary (CHO) cells are the most commonly used host for biopharmaceutical production. Although transcription and translation strategies have been employed to generate highly productive cell clones, secretion still remains a bottleneck for cellular productivity. By targeting the secretory pathway at multiple levels using synthetic biology tools, we aim to generate highly productive cell lines with predictable performance at an industrially relevant scale.
We employ an interdisciplinary approach combining 2D and 3D cell culture including primary cells from mice and humans, biochemistry, advanced microscopic techniques e.g. TIRF, FRET, and FRAP, image-based high-throughput screening, and in vivo mouse models.
Funded H2020 (MSCA 2019) project: SECRET - A MARIE SKŁODOWSKA-CURIE ACTIONS (MSCA) Innovative Training Network (ITN)
We will be exploring the SECRETory pathway regulation and its contribution to cancer by providing a highly qualified platform for European research training of bright young scientists, with the aim of defining secretory pathway-linked candidate biomarker genes suitable for cancer diagnosis and prognosis.
For details, check out the SECRET-ITN website: https://secret-itn.eu/
Our team welcomes Kerstin Ruoff and Sara Suárez López!
Kerstin will focus in her collaborative project with Boehringer Ingelheim Pharma GmbH & Co KG and Yokogawa Insilico Biotechnology on the production of genetically engineered CHO cells with improved titer and specific productivity through the development of novel methods and strategies for fine‐tuned control of the unfolded protein response.
We are excited you are here, and we look forward to working with you!
- Protein Kinase D promotes activity-dependent AMPA receptor endocytosis in hippocampal neurons. Oueslati Morales CO, Ignácz A, Bencsik N, Sziber Z, Rátkai AE, Lieb WS, Eisler SA, Szűcs A, Schlett K, Hausser A. Traffic. 2021 Sep 26. doi: 10.1111/tra.12819. Online ahead of print.
- Nucleobindin-1 regulates ECM degradation by promoting intra-Golgi trafficking of MMPs. Pacheco-Fernandez N, Pakdel M, Blank B, Sanchez-Gonzalez I, Weber K, Tran ML, Hecht TK, Gautsch R, Beck G, Perez F, Hausser A, Linder S, von Blume J. J Cell Biol. 2020 Aug 3;219(8):e201907058. doi: 10.1083/jcb.201907058. PMID: 32479594
- Deletion of Protein Kinase D3 Promotes Liver Fibrosis in Mice. Zhang S, Liu H, Yin M, Pei X, Hausser A, Ishikawa E, Yamasaki S, Jin ZG. Hepatology. 2020 Nov;72(5):1717-1734. doi: 10.1002/hep.31176. PMID: 32048304
- Cancer Cells Employ Nuclear Caspase-8 to Overcome the p53-Dependent G2/M Checkpoint through Cleavage of USP28. Müller I, Strozyk E, Schindler S, Beissert S, Oo HZ, Sauter T, Lucarelli P, Raeth S, Hausser A, Al Nakouzi N, Fazli L, Gleave ME, Liu H, Simon HU, Walczak H, Green DR, Bartek J, Daugaard M, Kulms D. Mol Cell. 2020 Mar 5;77(5):970-984.e7. doi: 10.1016/j.molcel.2019.12.023. PMID: 31982308
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Prof. Dr. Angelika Hausser (apl.), Lab head
Raluca Tamas, PhD (Program manager SECRET-ITN)
Kerstin Ruoff, PhD (Postdoctoral Researcher)
Elena Gutiérrez Galindo, PhD student
Zeynep Hazal Yilmaz, PhD student
Sara Suárez López, PhD Student
Gisela Link, Technical assistant
Ann-Kathrin Löffler, Master Student
Jan Alexander Schlegel, Master Student
Ines Schneider, Bachelor Student
Applications of students and scientists interested in signal transduction and membrane trafficking, and joining our team are always welcome! Please send your CV and a short summary of your research interests to Angelika Haußer.